Inter-oxa-13,14-dihydro-9β-PGD1 compounds

ABSTRACT

Prostaglandin analogs with the following cyclopentane ring structure: ##STR1## are disclosed along with intermediates useful in their preparation and processes for their preparation. These analogs are useful for the same pharmacological purposes as the prostaglandins, particularly and especially as blood platelet aggregation inhibitors.

The present application is a divisional application of Ser. No. 614,242,filed Sept. 17, 1975, now issued as U.S. Pat. No. 4,016,184, on Apr. 5,1977.

The present invention relates to prostaglandin analogs for which theessential material constituting a disclosure therefor is incorporated byreference here from U.S. Pat. No. 4,016,184, issued Apr. 5, 1977.

I claim:
 1. A prostaglandin analog of the formula ##STR2## wherein Y iscis--CH═CH-- or trans--CH═CH--; wherein m is one to 5, inclusive;wherein M₁ is ##STR3## or ##STR4## wherein R₅ and R₆ are hydrogen ormethyl, with the proviso that one of R₅ and R₆ is methyl only when theother is hydrogen;Wherein L₁ is ##STR5## or a mixture of ##STR6## and##STR7## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being thesame or different, with the proviso that one of R₃ and R₄ is fluoro onlywhen the other is hydrogen or fluoro; Wherein R₁ is hydrogen, alkyl ofone to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms,inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenylsubstituted with one, two, or three chloro or alkyl of one to 3 carbonatoms, inclusive, or a pharmacologically acceptable cation; and WhereinZ₈ is(1) --CH₂ --O--CH₂ --(CH₂)_(g) --CH₂ --, (2) --(ch₂)₂--o--(ch₂)_(g) --CH₂ --, or (3) --(CH₂)₃ --O--(CH₂)_(g) --,Wherein g isone, 2, or
 3. 2. A compound according to claim 1, wherein M₁ is ##STR8##3. A compound according to claim 1, wherein M₁ is ##STR9##
 4. A compoundaccording to claim 3, wherein Y is cis--CH═CH--.
 5. A compound accordingto claim 4, wherein m is
 3. 6. A compound according to claim 5, whereing is
 3. 7. 2a,2b-Dihomo-5-oxa-9β-15-epi-cis-13-PGD₁, a compoundaccording to claim
 6. 8. A compound according to claim 5, wherein g isone.
 9. 5-Oxa-9β-15-epi-cis-13-PGD₁, a compound according to claim 8.10. 3-Oxa-9β-15-epi-cis-13-PGD₁, a compound according to claim
 8. 11. Acompound according to claim 3, wherein Y is trans--CH═CH--.
 12. Acompound according to claim 11, wherein m is
 3. 13. A compound accordingto claim 12, wherein Z₈ is

    --CH.sub.2 --O--CH.sub.2 --(CH.sub.2).sub.g --CH.sub.2 --.


14. A compound according to claim 13, wherein g is
 3. 15. A compoundaccording to claim 13, wherein g is one.
 16. A compound according toclaim 15, wherein R₅ and R₆ are both hydrogen.
 17. A compound accordingto claim 16, wherein R₃ and R₄ are both hydrogen.
 18. 5-Oxa-9β-PGD₁, acompound according to claim
 17. 19. A compound according to claim 16,wherein R₃ and R₄ are both fluoro.
 20. 16,16-Difluoro-5-oxa-9β-PGD₁, acompound according to claim
 19. 21. A compound according to claim 12,wherein Z₈ is

    --(CH.sub.2).sub.3 --O--(CH.sub.2).sub.g --.


22. A compound according to claim 21, wherein g is
 3. 23. A compoundaccording to claim 22, wherein R₅ and R₆ are both hydrogen.
 24. Acompound according to claim 23, wherein R₃ and R₄ are both hydrogen. 25.2a,2b-Dihomo-3-oxa-9β-PGD₁, a compound according to claim
 24. 26. Acompound according to claim 23, wherein R₃ and R₄ are both fluoro. 27.2a,2b-Dihomo-16,16-difluoro-3-oxa-9β-PGD₁, a compound according to claim26.
 28. A compound according to claim 21, wherein g is one.
 29. Acompound according to claim 28, wherein R₅ and R₆ are both hydrogen. 30.A compound according to claim 29, wherein R₃ and R₄ are both hydrogen.31. 3-oxa-9β-PGD₁, a compound according to claim
 30. 32. A compoundaccording to claim 29, wherein R₃ and R₄ are both fluoro. 33.16,16-Difluoro-5-oxa-9β-PGD₁, a compound according to claim 32.